Identification of Compounds Protecting Pancreatic Islets against Oxidative Stress using a 3D Pseudoislet Screening Platform.

Autor: Rademakers T; Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, 6229 ER, the Netherlands., Sthijns MMJPE; Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, 6229 ER, the Netherlands.; Food Innovation and Health, Department of Human Biology, Maastricht University, Venlo, 5911 BV, the Netherlands., Paulino da Silva Filho O; Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, 6229 ER, the Netherlands., Joris V; Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, 6229 ER, the Netherlands., Oosterveer J; Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, 6229 ER, the Netherlands., Lam TW; Pivot Park Screening Centre (PPSC), Oss, 5349 AB, the Netherlands., van Doornmalen E; Pivot Park Screening Centre (PPSC), Oss, 5349 AB, the Netherlands., van Helden S; Pivot Park Screening Centre (PPSC), Oss, 5349 AB, the Netherlands., LaPointe VLS; Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, 6229 ER, the Netherlands.
Jazyk: angličtina
Zdroj: Advanced biology [Adv Biol (Weinh)] 2023 Dec; Vol. 7 (12), pp. e2300264. Date of Electronic Publication: 2023 Aug 11.
DOI: 10.1002/adbi.202300264
Abstrakt: Oxidative stress leads to a lower success rate of clinical islet transplantation. Here, FDA-approved compounds are screened for their potential to decrease oxidative stress and to protect or enhance pancreatic islet viability and function. Studies are performed on in vitro "pseudoislet" spheroids, which are pre-incubated with 1280 different compounds and subjected to oxidative stress. Cell viability and oxidative stress levels are determined using a high-throughput fluorescence microscopy pipeline. Initial screening on cell viability results in 59 candidates. The top ten candidates are subsequently screened for their potential to decrease induced oxidative stress, and eight compounds efficient reduction of induced oxidative stress in both alpha and beta cells by 25-50%. After further characterization, the compound sulfisoxazole is found to be the most capable of reducing oxidative stress, also at short pre-incubation times, which is validated in primary human islets, where low oxidative stress levels and islet function are maintained. This study shows an effective screening strategy with 3D cell aggregates based on cell viability and oxidative stress, which leads to the discovery of several compounds with antioxidant capacity. The top candidate, sulfisoxazole is effective after a 30 min pre-incubation, maintains baseline islet function, and may help alleviate oxidative stress in pancreatic islets.
(© 2023 The Authors. Advanced Biology published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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